Scientists Spot New Cholesterol-Lowering Target

Mice without a key protein cut their "bad" cholesterol in half

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FRIDAY, April 1, 2005 (HealthDay News) -- Researchers say they've identified a protein that could be a new target for the development of cholesterol-lowering drugs.

A team at the University of Texas Southwestern Medical Center at Dallas studied mice engineered to lack the Pcsk9 gene, which expresses a cholesterol-linked protein called PCSK9.

This protein normally disposes of cell receptors in the liver that latch onto -- and eliminate -- the "bad" low-density lipoprotein (LDL) cholesterol. Mice lacking this protein held on to more of these LDL receptors, the researchers explained, allowing the receptors to take up more LDL cholesterol from the blood.

Compared with normal mice, mice unable to produce PCSK9 cut their blood level of LDL cholesterol in half, the researchers reported this week in the online edition of Proceedings of the National Academy of Sciences.

Humans also have the PCSK9 protein, they noted.

"The expression of LDL receptors is the primary mechanism by which humans lower LDL cholesterol in the blood," senior author Dr. Jay Horton, associate professor of internal medicine, said in a prepared statement.

"This research shows that in mice, deleting the PCSK9 protein results in an increase in LDL receptors and a significant lowering of LDL cholesterol," he said.

High LDL cholesterol contributes to the buildup of plaque in the arteries and is a major risk factor for heart disease, heart attack and stroke.

Previous research found that humans with mutations in the Pcsk9 gene that prevented them from producing normal levels of PCSK9 had LDL cholesterol levels 40 percent below those of people without the mutation.

"The lower cholesterol levels of humans with mutations in Pcsk9, combined with the results of our studies in mice, suggest that variations in the levels of the PCSK9 protein significantly affect blood cholesterol levels, and compounds that inhibit this protein may be useful for the treatment of high cholesterol," Horton said.

More information

The American Heart Association has more about cholesterol.

SOURCE: University of Texas Southwestern Medical Center at Dallas, news release, March 29, 2005

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